Regulation of Laboratory-Developed Tests in Preventive Oncology: Emerging Needs and Opportunities.

Cancer predictive or diagnostic assays, offered as Laboratory-Developed Tests (LDTs), have been subject to regulatory authority and enforcement discretion by the US Food and Drug Administration. Many LDTs enter the market without US Food and Drug Administration or any regulatory review. The Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Amendments focuses on analytic performance, but has limited oversight of the quality or utility of LDTs, including whether patients have been harmed as a result of their use. Increasingly, LDTs for cancer risk or early detection have been marketed directly to consumers, with many LDT developers depicting these tests, requested by patients but ordered by personal or company-associated physicians, as procedures falling under the practice of medicine. This patchwork of regulation and enforcement uncertainty regarding LDTs and public concerns about accuracy of tests given emergency authorization during the COVID-19 pandemic led to the Verifying Accurate Leading-edge IVCT (in vitro clinical test) Development Act of 2021. This pending federal legislation represents an opportunity to harmonize regulatory policies and address growing concerns over quality, utility, and safety of LDTs for cancer genomics, including tests marketed directly to consumers. We review here questions regarding the potential benefits and harms of some cancer-related LDTs for cancer risk and presymptomatic molecular diagnosis, increasingly marketed to oncologists or directly to the worried well. We offer specific proposals to strengthen oversight of the accuracy and clinical utility of cancer genetic testing to ensure public safety.

Achieving universal genetic assessment for women with ovarian cancer: Are we there yet? A systematic review and meta-analysis.

PURPOSE: Several professional organizations recommend universal genetic assessment for people with ovarian cancer as identifying pathogenic variants can affect treatment, prognosis, and all-cause mortality for patients and relatives. We sought to evaluate the literature on genetic assessment for women with ovarian cancer and determine if any interventions or patient characteristics drive utilization of services. METHODS: We searched key electronic databases to identify trials that evaluated genetic assessment for people with ovarian cancer. Trials with the primary aim to evaluate utilization of genetic assessment with or without interventions were included. Eligible trials were subjected to meta-analysis and the moderating influence of health interventions on rates of genetic assessment were examined. RESULTS: A total of 35 studies were included (19 report on utilization of genetic services without an intervention, 7 with an intervention, and 9 with both scenarios). Without an intervention, pooled estimates for referral to genetic counseling and completion of genetic testing were 39% [CI 27-53%] and 30% [CI 19-44%]. Clinician-facilitated interventions included: mainstreaming of genetic services (99% [CI 86-100%]), telemedicine (75% [CI 43-93%]), clinic-embedded genetic counselor (76% [CI 32-95%]), reflex tumor somatic genetic assessment (64% [CI 17-94%]), universal testing (57% [28-82%]), and referral forms (26% [CI 10-53%]). Random-effects pooled proportions demonstrated that Black vs. White race was associated with a lower rate of genetic testing (26%[CI 17-38%] vs. 40% [CI 25-57%]) as was being un-insured vs. insured (23% [CI 18-28%] vs. 38% [CI 26-53%]). CONCLUSIONS: Reported rates of genetic testing for people with ovarian cancer remain well below the goal of universal testing. Interventions such as mainstreaming can improve testing uptake. Strategies aimed at improving utilization of genetic services should consider existing disparities in race and insurance status.

Effects of socioeconomic status and treatment disparities in colorectal cancer survival.

BACKGROUND: Poor survival among colorectal cancer (CRC) cases has been associated with African-American race and low socioeconomic status (SES). However, it is not known whether the observed poor survival of African-American CRC cases is due to SES itself and/or treatment disparities. We set out to determine this using data from the large, population-based California Cancer Registry database. METHODS: A case-only analysis of CRC was conducted including all age groups using California Cancer Registry data from 1994 to 2003, including descriptive analysis of relevant clinical variables, race, and SES. CRC-specific survival univariate analyses were conducted using the Kaplan-Meier method. Multivariate survival analyses were done using Cox proportional hazards ratios (HR). RESULTS: Incident cases of colon (90,273) and rectal (37,532) cancer were analyzed, including 91,739 (71.8%) non-Hispanic Whites, 8,535 (6.7%) African-Americans, 14,943 (11.7%) Hispanics, 3,564 (2.8%) Chinese, and 7,950 (6.2%) non-Chinese Asians. African-Americans had a greater proportion of metastatic stage at presentation (P < 0.0001) and decreased CRC-specific survival (P < 0.0001 for colon and rectal cancer). After adjustment for age, sex, histology, site within the colon, and stage, African-Americans [colon: HR, 1.19; 95% confidence interval (95% CI), 1.14-1.25; rectum: HR, 1.27; 95% CI, 1.17-1.38] had an increased risk of death compared with Caucasians. However, after further adjustment for SES and treatment, the risk of death for African-Americans compared with Caucasians was substantially diminished (colon: HR, 1.08; 95% CI, 1.03-1.13; rectum: HR, 1.11; 95% CI, 1.02-1.20). CONCLUSION: Among CRC cases, disparities in treatment and SES largely explain the observed decreased survival of African-Americans, underscoring the importance of health disparity research in this disease.

Race, socioeconomic status, treatment, and survival time among pancreatic cancer cases in California.

BACKGROUND: Poor survival in pancreatic adenocarcinoma is associated with African-American race and also with low socioeconomic status (SES). However, it is not known whether the observed poor survival of African-American pancreatic adenocarcinoma cases is due to SES itself and/or treatment disparities. We set out to determine this using the large, population-based California Cancer Registry (CCR) database as a model. METHODS: We conducted a case-only analysis of CCR data (1989-2003), including descriptive analysis of relevant clinical variables and SES. The SES variable used has been derived from principle component analysis of census block level CCR data linked to census data to address seven major indicators of SES. Overall survival univariate analyses were conducted using the Kaplan-Meier method. Multivariate survival analyses were done using Cox proportional hazards ratios (HR). RESULTS: Incident cases of pancreatic cancer (24,735) were analyzed. Among adenocarcinomas, after adjustment for age, year of diagnosis, and gender, African-Americans [HR, 1.14; 95% confidence interval (95% CI), 1.08-1.21] and Hispanics (HR, 1.06; 95% CI, 1.01-1.11) had an increased risk of death compared with Caucasians. These differences persisted after adjustment for stage. However, after further adjustment for SES, surgery, radiation, and chemotherapy, the risk of death for African-Americans (HR, 1.00; 95% CI, 0.94-1.06) and Hispanics (HR, 0.97; 95% CI, 0.93-1.02) was not statistically different from Caucasians. CONCLUSIONS: Differences in treatment and SES likely account for the observed poor survival of African-Americans and Hispanics among pancreatic adenocarcinoma cases. These data highlight the importance of improving access to care for ethnic minority pancreatic cancer patients.